Prognostic significance of immunohistochemical proliferation markers (Ki-67/MIB-1 and proliferation-associated nuclear antigen), p53 protein accumulation, and neovascularization in clinical stage A nonseminomatous testicular germ cell tumors

P. Albers, A. Orazi, T. M. Ulbright, G. A. Miller, J. H. Haidar, J. P. Donohue, R. S. Foster

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27 Scopus citations


Histopathologic features alone fail to reliably stratify patients with clinical Stage A nonseminomatous germ cell tumors of the testis into groups with high and low risk for occult metastatic disease. Previous flow cytometric studies at Indiana University demonstrated a significant correlation between high proliferative activity and metastatic disease. The current study evaluated the prognostic significance of immunohistochemical markers related to tumor proliferation and aggressiveness in a consecutive series of clinical Stage A nonseminomatous germ cell tumors patients who underwent retroperitoneal lymph node dissection. Archival material of the orchiectomy specimens of 62 patients (45 pathologic Stage A, 17 with metastatic disease) was reviewed and immunohistochemically stained for Ki-67 antigen (MIB-1), proliferation-associated nuclear antigen (PC10), p53 protein (Pab1801), and Factor-VIII-related antigen (neovascularization). Staining with MIB-1 was significantly higher in the metastatic group (mean 80.2%, standard deviation [SD] 15.5) than in pathologic Stage A cases (66.3%, SD 27.9; P = 0.0032) and was predictive of metastatic status with a sensitivity of 82% and specificity of 69%. In this study, no patient with a MIB-1 value less than 52% had metastases. Proliferation-associated nuclear antigen and p53 staining correlated with MIB-1 values (R = 0.63 and 0.55, respectively) but did not correlate with metastatic status. Tumor angiogenesis was also not predictive of metastatic status. Assessment of proliferation rates using MIB-1 antibody in clinical Stage A nonseminomatous germ-cell-tumor patients may prove helpful in predicting metastatic status. A subgroup of patients with very low proliferation rates may especially benefit from MIB-1 analysis, because they were at very low risk for metastatic disease. Proliferation-associated nuclear antigen, p53 expression, and neovascularization were not able to discriminate between cases with add without metastases.

Original languageEnglish (US)
Pages (from-to)492-497
Number of pages6
JournalModern Pathology
Issue number5
StatePublished - Jan 1 1995



  • Immunohistochemistry
  • Ki-67
  • Nonseminomatous testicular germ cell tumor
  • p53
  • Prognosis
  • Staging

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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